1. Field of the Invention
The present invention describes methods for obtaining useful steroids such as progesterone.
2. Description of the Art
This invention deals basically with the conversion of steroid compounds having an acid side chain to give useful intermediates and end compounds such as progesterone.
For instance, in published European patent application 4-913 dated Oct. 31, 1979, it was revealed that through microbiological transformation that it was possible to obtain a substantial yield of steroids having a 20 carbonyl functionality. It has also been observed that through following the teachings of the European patent that it is also possible to obtain 3-oxo-pregna-1,4,17(20)-triene-20-carboxylic acid. Of course, depending upon the pH of the solution, it is possible to obtain the carbonyl compounds as either the acid or salt or mixtures thereof.
Jiu, et al, in U.S. Pat. No. 3,994,933, issued Nov. 30, 1976, describes the process of obtaining 3-oxo-pregna-4,17(20)-diene-20-carboxylic acid and its esters through microbiological degradation of several basic sterols. Previously, Julian in JACS Vol. 70, published Apr. 3, 1948, No. 3, at page 887, describes several steroids having an acid functionality in the side chain. Steroidal acids and their derivatives are discussed in U.S. Pat. No. 4,088,760 issued to Benson, et al., on May 9, 1978.
Derivatives of steroids are discussed in U.S. Pat. No. 2,566,336 issued to Julian, et al., Sept. 4, 1951, and in British Pat. No. 1,043,018 to Meyer, et al., published Sept. 21, 1966. Ruschig, et al, discusses steroids in U.S. Pat. No. 2,731,461 issued Jan. 17, 1956, and in an article published Feb. 21, 1955, in Chemische Berichte Jahrg.88, Number 6, 1955, pages 883-894. Additional steroid products are discussed in U.S. Pat. No. 2,752,369 issued to Holysz et al, on June 26, 1956 and U.S. Pat. No. 3,519,658 issued July 7, 1970 to Adam, et al.
Still more steroids are reported in "The Oxidation of Steroidal Amines to Nitro Steroids" by Robinson, et al, Volume 31, J. Am. Chem. Soc. 1956, p.524 et seq. A second article discussing amine steroids is found at Tetrahedron Letters, No. 18, pp. 1053-1061 (1964) by Tomita, et al. Amines are generally discussed by Corey, et al, J. Am. Chem. Soc., Vol. 91, #6, pp. 1429-32 (1969), and by Dinizo, et al, at J. Am. Chem. Soc., Vol. 97 #23, pp. 6900-6901 (1975).
Additional references which discuss compounds having acid side chains and their conversion into useful steroids include the article of Wieland, et al, published in Helvetica Chimica Acta, Vol. 32, part V (1949) No. 233 at page 1764. In another article in the same journal, steroids having an acid side chain are described by Meystre, et al, at Helvetica Chimica Acta, Vol. 32, part V (1949) No. 232 at page 1758. Similarly, Wieland, et al, at Helvetica Chimica Acta, Vol. 32, Part VI, (1949, No. 255 at page 1922 again describes the transformation of steroids having an acid side chain.
To the extent that each of the foregoing references are applicable to the present invention, they are herein incorporated by reference.
Throughout the present invention, percentages and ratios are given by weight unless otherwise indicated and temperatures are in degrees Celsius unless otherwise indicated.